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Construction of Aptamer‐siRNA Chimera/PEI/5‐FU/Carbon Nanotube/Collagen Membranes for the Treatment of Peritoneal Dissemination of Drug‐Resistant Gastric Cancer
- Source :
- Advanced Healthcare Materials. 9:2001153
- Publication Year :
- 2020
- Publisher :
- Wiley, 2020.
-
Abstract
- Due to extensive metastasis, poor blood supply, and drug-resistant, there is still no effective clinical means to treat peritoneal dissemination of gastric cancer. Here, an aptamer-siRNA chimera (Chim)/polyethyleneimine (PEI)/5-fluorouracil (5-FU)/carbon nanotube (CNT)/collagen membrane is constructed, which could be divided into 15 layers with a thickness of 70-100 µm. Sustained release experiments show that the collagen membranes can control 5-FU release for more than 2 weeks. Aptamer-siRNA chimera can specifically bind to gastric cancer cells, enabling targeted delivery of 5-FU and silencing drug-resistant gene. In vitro experiments demonstrated that Chim/PEI/5-FU/CNT nanoparticles promoted the apoptosis of 5-FU-resistant gastric cancer cells, inhibited their invasion and proliferation. Animal experiments show that Chim/PEI/5-FU/CNT/collagen membrane significantly inhibits the expression of mitogen-activated protein kinase (MAPK), and effectively treats peritoneal dissemination of 5-FU-resistant gastric cancer. Compared with siRNA/PEI/5-FU/CNT group, ki-67 proliferation index, and matrix metallopeptidase 9 (MMP9) expression are significantly decreased in the Chim/PEI/5-FU/CNT group, while the proportion of apoptotic cells is markly increased. In conclusion, a chimera/PEI/5-FU/CNT/collagen membrane is constructed, which can effectively treat peritoneal dissemination of drug-resistant gastric cancer. The study provides a new therapeutic approach for relevant clinical treatment.
- Subjects :
- MAPK/ERK pathway
Proliferation index
Biomedical Engineering
Pharmaceutical Science
02 engineering and technology
MMP9
010402 general chemistry
01 natural sciences
Metastasis
Biomaterials
Stomach Neoplasms
Cell Line, Tumor
medicine
Animals
Polyethyleneimine
Gene silencing
RNA, Small Interfering
Nanotubes, Carbon
Chemistry
021001 nanoscience & nanotechnology
medicine.disease
In vitro
0104 chemical sciences
Pharmaceutical Preparations
Apoptosis
Cancer cell
Cancer research
Collagen
Fluorouracil
0210 nano-technology
Subjects
Details
- ISSN :
- 21922659 and 21922640
- Volume :
- 9
- Database :
- OpenAIRE
- Journal :
- Advanced Healthcare Materials
- Accession number :
- edsair.doi.dedup.....ed933294ad04ca597c43946acf046fb5